The overall objective of the project is to evaluate a particular molecular model chemcial carcinogenesis and cocarcinogenesis for relevance in developing predictive molecular assay for compounds causing or influencing induction of cancer. The model stems for our current work on the molecular basis of cocarcinogenesis in rat embryo cell cultures. We have found evidence to suggest that activation of a specific set of genes is required before neoplastic transformation can be induced in these cells by carcinogens. Certain viral agents can activate these genes and thereby sensitive cells to the transforming action of mutagenic carcinogens. We will determine the response of various rat cells to selected examples of known and suspected carcinogens, tumor promoters, and permissive cocarcinogens, in terms of: transformation-related gene activation, measured by nucleic acid hybridization; effects on neoplastic transformation, in terms of cell morphology and growth behavior; and somatic mutation rates, measured in two different genetic loci unrelated to transformation. We will also examine tumor systems in which the transformation-related genes are known to be activated to determine whether these genes must be activated prior to tumor initiation.